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Glutathione infusion before primary percutaneous coronary intervention: a randomised controlled pilot study
OBJECTIVE: In the setting of reperfused ST-elevation myocardial infarction (STEMI), increased production of reactive oxygen species (ROS) contributes to reperfusion injury. Among ROS, hydrogen peroxide (H(2)O(2)) showed toxic effects on human cardiomyocytes and may induce microcirculatory impairment...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701599/ https://www.ncbi.nlm.nih.gov/pubmed/31399448 http://dx.doi.org/10.1136/bmjopen-2018-025884 |
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author | Tanzilli, Gaetano Truscelli, Giovanni Arrivi, Alessio Carnevale, Roberto Placanica, Attilio Viceconte, Nicola Raparelli, Valeria Mele, Rita Cammisotto, Vittoria Nocella, Cristina Barillà, Francesco Lucisano, Luigi Pennacchi, Mauro Granatelli, Antonino Dominici, Marcello Basili, Stefania Gaudio, Carlo Mangieri, Enrico |
author_facet | Tanzilli, Gaetano Truscelli, Giovanni Arrivi, Alessio Carnevale, Roberto Placanica, Attilio Viceconte, Nicola Raparelli, Valeria Mele, Rita Cammisotto, Vittoria Nocella, Cristina Barillà, Francesco Lucisano, Luigi Pennacchi, Mauro Granatelli, Antonino Dominici, Marcello Basili, Stefania Gaudio, Carlo Mangieri, Enrico |
author_sort | Tanzilli, Gaetano |
collection | PubMed |
description | OBJECTIVE: In the setting of reperfused ST-elevation myocardial infarction (STEMI), increased production of reactive oxygen species (ROS) contributes to reperfusion injury. Among ROS, hydrogen peroxide (H(2)O(2)) showed toxic effects on human cardiomyocytes and may induce microcirculatory impairment. Glutathione (GSH) is a water-soluble tripeptide with a potent oxidant scavenging activity. We hypothesised that the infusion of GSH before acute reoxygenation might counteract the deleterious effects of increased H(2)O(2) generation on myocardium. METHODS: Fifty consecutive patients with STEMI, scheduled to undergo primary angioplasty, were randomly assigned, before intervention, to receive an infusion of GSH (2500 mg/25 mL over 10 min), followed by drug administration at the same doses at 24, 48 and 72 hours elapsing time or placebo. Peripheral blood samples were obtained before and at the end of the procedure, as well as after 5 days. H(2)O(2) production, 8-iso-prostaglandin F2α (PGF2α) formation, H(2)O(2) breakdown activity (HBA) and nitric oxide (NO) bioavailability were determined. Serum cardiactroponin T (cTpT) was measured at admission and up to 5 days. RESULTS: Following acute reperfusion, a significant reduction of H(2)O(2) production (p=0.0015) and 8-iso-PGF2α levels (p=0.0003), as well as a significant increase in HBA (p<0.0001)and NO bioavailability (p=0.035), was found in the GSH group as compared with placebo. In treated patients, attenuated production of H(2)O(2) persisted up to 5 days from the index procedure (p=0.009) and these changes was linked to those of the cTpT levels (r=0.41, p=0.023). CONCLUSION: The prophylactic and prolonged infusion of GSH seems to determine a rapid onset and persistent blunting of H(2)O(2) generation improving myocardial cell survival. Nevertheless, a larger trial, adequately powered for evaluation of clinical endpoints, is ongoing to confirm the current finding. TRIAL REGISTRATION NUMBER: EUDRACT 2014-00448625; Pre-results. |
format | Online Article Text |
id | pubmed-6701599 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-67015992019-09-02 Glutathione infusion before primary percutaneous coronary intervention: a randomised controlled pilot study Tanzilli, Gaetano Truscelli, Giovanni Arrivi, Alessio Carnevale, Roberto Placanica, Attilio Viceconte, Nicola Raparelli, Valeria Mele, Rita Cammisotto, Vittoria Nocella, Cristina Barillà, Francesco Lucisano, Luigi Pennacchi, Mauro Granatelli, Antonino Dominici, Marcello Basili, Stefania Gaudio, Carlo Mangieri, Enrico BMJ Open Cardiovascular Medicine OBJECTIVE: In the setting of reperfused ST-elevation myocardial infarction (STEMI), increased production of reactive oxygen species (ROS) contributes to reperfusion injury. Among ROS, hydrogen peroxide (H(2)O(2)) showed toxic effects on human cardiomyocytes and may induce microcirculatory impairment. Glutathione (GSH) is a water-soluble tripeptide with a potent oxidant scavenging activity. We hypothesised that the infusion of GSH before acute reoxygenation might counteract the deleterious effects of increased H(2)O(2) generation on myocardium. METHODS: Fifty consecutive patients with STEMI, scheduled to undergo primary angioplasty, were randomly assigned, before intervention, to receive an infusion of GSH (2500 mg/25 mL over 10 min), followed by drug administration at the same doses at 24, 48 and 72 hours elapsing time or placebo. Peripheral blood samples were obtained before and at the end of the procedure, as well as after 5 days. H(2)O(2) production, 8-iso-prostaglandin F2α (PGF2α) formation, H(2)O(2) breakdown activity (HBA) and nitric oxide (NO) bioavailability were determined. Serum cardiactroponin T (cTpT) was measured at admission and up to 5 days. RESULTS: Following acute reperfusion, a significant reduction of H(2)O(2) production (p=0.0015) and 8-iso-PGF2α levels (p=0.0003), as well as a significant increase in HBA (p<0.0001)and NO bioavailability (p=0.035), was found in the GSH group as compared with placebo. In treated patients, attenuated production of H(2)O(2) persisted up to 5 days from the index procedure (p=0.009) and these changes was linked to those of the cTpT levels (r=0.41, p=0.023). CONCLUSION: The prophylactic and prolonged infusion of GSH seems to determine a rapid onset and persistent blunting of H(2)O(2) generation improving myocardial cell survival. Nevertheless, a larger trial, adequately powered for evaluation of clinical endpoints, is ongoing to confirm the current finding. TRIAL REGISTRATION NUMBER: EUDRACT 2014-00448625; Pre-results. BMJ Publishing Group 2019-08-08 /pmc/articles/PMC6701599/ /pubmed/31399448 http://dx.doi.org/10.1136/bmjopen-2018-025884 Text en © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Cardiovascular Medicine Tanzilli, Gaetano Truscelli, Giovanni Arrivi, Alessio Carnevale, Roberto Placanica, Attilio Viceconte, Nicola Raparelli, Valeria Mele, Rita Cammisotto, Vittoria Nocella, Cristina Barillà, Francesco Lucisano, Luigi Pennacchi, Mauro Granatelli, Antonino Dominici, Marcello Basili, Stefania Gaudio, Carlo Mangieri, Enrico Glutathione infusion before primary percutaneous coronary intervention: a randomised controlled pilot study |
title | Glutathione infusion before primary percutaneous coronary intervention: a randomised controlled pilot study |
title_full | Glutathione infusion before primary percutaneous coronary intervention: a randomised controlled pilot study |
title_fullStr | Glutathione infusion before primary percutaneous coronary intervention: a randomised controlled pilot study |
title_full_unstemmed | Glutathione infusion before primary percutaneous coronary intervention: a randomised controlled pilot study |
title_short | Glutathione infusion before primary percutaneous coronary intervention: a randomised controlled pilot study |
title_sort | glutathione infusion before primary percutaneous coronary intervention: a randomised controlled pilot study |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701599/ https://www.ncbi.nlm.nih.gov/pubmed/31399448 http://dx.doi.org/10.1136/bmjopen-2018-025884 |
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